Human Response to Future Flu Pandemic Must Be Swift, Experts Say at AAAS

Joe Palca, Rajeev Venkayya, and Julie E. Fischer

While the United States and other nations are preparing for a possible global flu pandemic, health authorities would have to act within about two weeks to have much hope of preventing the rapid spread of a newly emergent flu virus, a specialist on global health said at a 19 November AAAS panel discussion.

Julie E. Fischer, who leads the Henry L. Stimson Center's program on global health security, said that even optimistic mathematical models on the rate of transmission of the disease in Southeast Asia give little room for delay. She cited a model, based on predicted transmission rates in rural Thailand, which suggests health authorities would have to institute rapid response measures—such as bringing in large amounts of anti-viral medications—within 14 to 21 days to have a chance of slowing or halting the spread of the disease.

Even with quick intervention, the prospects of success would be uncertain, according to Dr. Rajeev Venkayya, former special assistant to President George W. Bush on bio-defense issues. "The chances of this working are really quite small," Venkayya said during a discussion on managing a pandemic. "It sounds good, it looks good to mathematical modelers. But there are a lot of moving parts, there a lot of things that would have to fall into place for us to successfully quell such an outbreak."

Still, Venkayya said, any steps that slow or stop a virus would be worth the cost and effort. "The dividends are massive if you can be successful," he said.

The projected impact if a pandemic does occur is sobering. Extrapolating from previous pandemics, federal authorities have estimated that up to 2 million people might die in the United States during a severe influenza pandemic. Even a milder outbreak, similar to the 1957 Asian flu or the 1968 Hong Kong flu, could kill 100,000 or more Americans, the estimates suggest. Interventions not available during earlier pandemics could reduce the death toll, however.

The panel discussion on preparing for a pandemic was the third in a four-part series on "Science and Society: Grand Challenges," sponsored by the AAAS Center for Science, Technology and Security Policy; Georgetown University's Program on Science in the Public Interest; and the Smithsonian Institution's Lemelson Center for the Study of Invention and Innovation.

The real challenge, according to Fischer, is detecting an emerging flu threat rapidly enough to even attempt a response. She cited the difficulties containing the 2003 outbreak in Asia of severe acute respiratory syndrome (SARS), a viral respiratory illness. "The global spread of disease is no longer on a timetable that we can predict easily," Fischer said. In an age of air travel and widespread mobility, the SARS infection moved around the globe much more quickly than the devastating flu virus of 1918.

While Venkayya said he is troubled by the "overwhelming uncertainty" on how quickly a newly emergent flu virus might spread and behave, he and Fischer cited positive steps being taken by the World Health Organization (WHO) and national governments to prepare for the worst. WHO has been working with its member states to develop rapid response plans, Fischer said. New international health regulations require nations to develop the capacity to detect and respond to disease outbreaks with the potential for global transmission.

The United States and other nations have been providing resources to developing nations where the emergence of new flu strains from bird populations has occurred historically. The bilateral assistance plans include money to improve disease surveillance, laboratory capacity and emergency medical response.

The United States has invested just under half a billion dollars in international capacity-building, Venkayya said, accounting for about 25% of the worldwide effort. It is essential that such commitments be sustained and expanded in countries such as Indonesia, Thailand, and Vietnam where animal populations are known to harbor potentially dangerous flu strains, he said.

Joe Palca, a science correspondent for National Public Radio who moderated the discussion, asked whether additional funds will be forthcoming for pandemic preparedness.

"We have tended historically to do what I would call 'crisis disease response,' " Fischer said. "And that's to sort of lurch from outbreak to outbreak." If human-to-human transmission of a new flu strain does not occur readily, it is easy for people, and governments, to let their guard down, she said. There has been "message fatigue" apparent already in some of the marketplaces in Southeast Asia, she said, since the H5N1 strain of avian flu jumped to humans three years ago in a handful of cases. Poultry handlers who heeded public health messages initially often go back to their old, more casual practices, she said.

Some nations have resisted sharing virus samples isolated from flu victims with researchers in the United States and elsewhere. Indonesia withheld specimens this year on the grounds that they would be used to help developed nations produce vaccines primarily for use in developed nations. It is important to grapple with such equity issues, Venkayya said, and the U.S. should encourage vaccine stockpiles, tiered pricing plans, technology transfer and other steps to assure more access to vaccine in all nations. But he said it is essential that nations share their samples of flu virus isolates. Newly emergent strains represent a global threat, he said, and there must be a global response.

Asked by Palca about the status of flu vaccine development, Venkayya noted estimates that it would take about five months to produce the first doses of a vaccine tailored to a newly emergent flu strain. That means a new vaccine would miss the first wave of a pandemic. Existing vaccines might provide limited protection, he said, and there has been promising work using adjuvants, such as alum, to help stretch the number of doses available from a given lot of vaccine. But in an emergency, world vaccine capacity would be hard-pressed to keep up with demand. The current global flu vaccine output against seasonal forms of flu is 300 million doses per year, Venkayya said. There are efforts to develop new, more efficient cellular methods that would supplant use of chicken eggs as a growth medium for flu vaccines.

Antiviral medications also might help reduce the impact of the virus during the first 48 hours, as suggested by studies in mice, Venkayya said. But if drugs are not effective and a vaccine is not quickly available, the key to managing a pandemic will be other public health measures, such as reducing face-to-face contact by closing of schools, canceling of large public gatherings, limiting contact in the workplace through teleconferences and staggered work shifts. An organized, rapid response can have a significant impact on death rates, Venkayya said, citing evidence from the 1918 flu epidemic. During that outbreak, he said, St. Louis moved quickly to limit public gatherings and reduce face-to-face contacts while Philadelphia had a more delayed, disorganized response. A study published earlier this year in the Proceedings of the National Academy of Sciences found that cities responding quickly to the epidemic, such as St. Louis, had peak death rates that were about 50% lower than those of slower cities such as Philadelphia.

Even the best plans are of little help if they are not well-disseminated and the public does not understand them, Fischer said. Venkayya also stressed the need for clear messages to the public during a pandemic. "There needs to be strong leadership during a crisis of this nature," he said. "You need to have somebody in Washington or Atlanta getting out there and telling public health experts around across the country: This is the roadmap" for protecting your community. Without strong federal leadership, he added, there could be chaos, with thousands of communities doing their own thing. "That's what I lose sleep over," Venkayya said. It will be important for citizens to "ask the hard questions" of policy makers, he said, such as: "What's your plan? Who's going to be the spokesman in my community?"

Earl Lane

28 November 2007